Biomedical subjects

J Towfighi

Publications and source records attributed to J Towfighi.

At least 73 records · Page 4Linked to original sources

PubMed1989

Cerebral glycogenosis, alpha particle type: morphologic and biochemical observations in an infant.

A 3-month-old infant with congenital hypotonia suffering from an unusual form of glycogenosis is reported. The most striking neuropathologic findings were vacuolation of neuropile and glycogen accumulation, especially in the cerebral cortex and cerebellar molecular layer. Ultrastructurally, glycogen accumulation was present mainly in neurites and astrocytic processes, and mostly appeared as rosettes (alpha glycogen particles). Biochemical analysis of glycogen in various regions of the central nervous system showed an increase of up to 100-fold. The cerebral cortex, deep nuclei, and cerebellar cortex had the highest glycogen elevations, while the cerebral white matter glycogen level was normal. Among other tissues, the heart showed a several-fold increase in glycogen content. Muscle, liver, and kidney glycogen levels were not elevated. Findings in this case and in three other reported patients with cerebral glycogenosis of alpha particle type are discussed.

Brain↗

PubMed1989

Effect of dimethylsulfoxide on human gliomas: correlations between the nuclear magnetic resonance spectra and the transformed phenotypes of the tumor cells.

Prolonged in vitro induction of six established human glioma cell lines with dimethylsulfoxide (DMSO) generated an adherent human fibroblastoid phenotype. The development of contact-inhibited cell growth coincided with the decreased colony-forming potential of these cells in semisolid medium and with the reduction or elimination of tumorigenicity when transplanted in athymic nude mice. These DMSO-induced changes persisted for at least 19 passages after removal of the inducer from the medium. High-resolution natural-abundance 13C nuclear magnetic resonance spectroscopy showed specific spectral differences between the cell lines with more or less malignant transformed phenotypes: the glioma cells with a higher degree of tumorigenicity and colony-forming potential exhibited more intense myoinositol signals than those with the more benign phenotype.

Animals↗

PubMed1988

Neuronal lesions in mercaptopropionic acid-induced status epilepticus.

Neuropathological studies of rats were made after seizures of different durations. Seizures were produced by mercaptopropionic acid in paralyzed, ventilated rats that were perfusion-fixed immediately (acute) or after 2-7 days of recovery (chronic). Analysis of chronic rats, which had only 20-min seizures, showed that damage occurred to several structures including: the substantia nigra pars reticulata, the hypothalamus, the diagonal band of Broca, and the globus pallidus; the damage was worse with longer seizures. In rats perfused acutely no changes were detected in paraffin sections in the aforementioned structures if the length of seizures was 45 min or less. It was concluded that: (1) mercaptopropionic acid-induced seizures cause permanent lesions to specific brain areas, with the most pronounced effect in the substantia nigra pars reticulata; (2) the lesions result from the seizures, and they are roughly proportional to the seizures duration; and (3) permanent lesions may begin within 20 min but require longer times to become visible on light microscopy.

3-Mercaptopropionic Acid↗

PubMed1988

Creutzfeldt-Jakob disease following pituitary-derived human growth hormone therapy: a new American case.

A fourth histologically-confirmed American case of Creutzfeldt-Jakob disease (CJD) related to human growth hormone (hGH) therapy is reported. Like kuru, the illness was dominated by cerebellar signs and relatively little mental deterioration. The diagnosis was strongly supported premortem by the presence of two abnormal 30 kDa proteins in the CSF that are seen almost exclusively in CJD. The characteristic clinical picture coupled with such biochemical data allow a reasonably accurate premortem diagnosis of hGH-related iatrogenic CJD to be made.

Adult↗

PubMed1988

Clinical significance of types of cerebellar amyloid plaques in human spongiform encephalopathies.

We report three patients with both spongiform encephalopathy and cerebellar amyloid plaques; one showed kuru-like plaques and was diagnosed as having Creutzfeldt-Jakob disease (CJD), and two had multicentric plaques and were diagnosed as having Gerstmann-Sträussler-Scheinker disease (GSSD). Evaluation of these cases and review of others previously reported suggests a clinicopathologic correlation between type of cerebellar plaque and neurologic clinical course. CJD patients who showed kuru-like plaques generally had disease with early onset (average age, 49.1 years) and long duration (average, 34 months), as compared with CJD patients without kuru-like plaques. GSSD patients usually had multicentric cerebellar plaques, and cases were usually familial, had early age of onset (average, 42.7 years), and were of long duration (average, 73 months). Myoclonus was infrequent in GSSD patients and pathologically spongiform change was minimal; spinal tract degeneration was common.

Adult↗

PubMed1987

Autoimmune basis for visual paraneoplastic syndrome in patients with small cell lung carcinoma. Retinal immune deposits and ablation of retinal ganglion cells.

Recently, patients with visual paraneoplastic syndrome (VPS) were described, a binocular loss of vision found in patients with small cell carcinoma of the lung (SCCL). The patients have serum antibodies against a small number of discrete antigens which are shared by the retina and small cell carcinoma cells, and which are associated with cells and processes of the ganglion cell layer of the retina. Pathologic findings are presented with regard to the presence of immunoglobulins in, and the nature of the lesions in, the central nervous system of a VPS patient. The patient's blood-brain barrier was shown to be compromised, as demonstrated by the finding of high immunoglobulin levels in the cerebrospinal fluid and immune deposits in the retina. It is further shown that within the central nervous system only the retina and optic nerve show any tissue damage with the specific loss of retinal ganglion cells and their processes. The findings support the hypothesis of an autoimmune cause for this remote effect of cancer.

Aged↗

PubMed1987

Effect of differentiation inducers on growth characteristics of human glioma cell lines.

The effect of dimethylsulfoxide (DMSO) and iododeoxyuridine (IUdR) on the growth characteristics of two established human glioblastoma cell lines (FG and HMCN-1) was studied. The FG cell line has been characterized. The HMCN-1 cell line, established in our laboratory, consisted of fibroblastoid and polygonal cells that grew without contact inhibition. Subcutaneous injection of these cells into weanling athymic nude mice induced slowly growing, solid tumors that were histologically spindly with areas that were similar to the original tumor. Chromosomal analyses revealed a human heteroploid pattern with a modal number of 69. The cells of the original human glioma contained S-100 protein and glial fibrillary acidic protein (GFA protein), whereas the established cells failed to express markers. Prolonged treatment of glioma cells with DMSO generated a more adherent, normal human fibroblastoid phenotype that grew with contact inhibition. The new phenotype and proliferative restriction of these cells was evident as late as 50 days after discontinuation of treatment. The chemical induction of cell differentiation resulted in decreased tumorigenic potential in athymic nude mice.

Cell Differentiation↗

PubMed1987

Systemic deficiency of the first component of the pyruvate dehydrogenase complex.

An infant with lactic acidosis and developmental delay had neuropathological changes consistent with Leigh's necrotizing encephalomyelopathy. Total pyruvate dehydrogenase complex (PDC) activity was low relative to controls in lymphocytes (0.2 versus 1.9 +/- 0.6 SD nmol/min/mg protein) and cultured skin fibroblasts (0.9 versus 2.7 +/- 1.0). Liver, muscle, heart, and kidney mitochondria oxidized several substrates normally, but did not oxidize pyruvate. PDC activity was absent in these mitochondria (0.1 versus 9.8 +/- 4.2 in liver and 0.7 versus 75 +/- 26 in muscle) and was very low in all tissue homogenates. Activity of the first component was low in liver mitochondria, whereas activities of the second and third components were normal. Western blot analysis of tissue proteins showed normal amounts of second and third component of PDC but undetectable to trace amounts of both alpha and beta subunits of the first component of PDC in liver, brain, kidney, heart, and skin fibroblasts. Thus, profound systemic deficiency of PDC was due to lack of both subunit proteins of the first component of PDC.

Fibroblasts↗

PubMed1987

Purkinje cell inclusions and 'atelencephaly' in 13q-chromosomal syndrome.

Severe microcephaly was present from birth in a child with a 13q-chromosomal syndrome [46,XY,del(13)(q22q31)]. He died at 20 months of age. Neuropathologic findings included atelencephaly and eosinophilic cytoplasmic inclusions in cerebellar Purkinje cells. Ultrastructurally, the inclusions consisted of stacks of parallel cisternae separated by electron-dense granular material. The relationship between these inclusions and the smaller cytoplasmic inclusions known as "lamellar bodies" is discussed, and the central nervous system malformations in this syndrome are reviewed.

Chromosome Aberrations↗

PubMed1986

Hepatic damage in neonatal rat due to E. coli endotoxin.

Liver from neonatal rats injected with LD50 E. coli endotoxin was studied by light and electron microscopy. By 2 hr, there was margination and migration of polymorphonuclear leukocytes. Single cell necrosis was seen after 8 hr. At 16 hr, there were numerous necrotic foci in the mid-zonal region of hepatic lobules, as well as accumulation of microvesicular fat. Necrosis and fatty change of hepatocytes were more extensive at 24 hr. Microvesicular fat accumulation may be related to alterations in fatty acid or oxidative metabolism. However, the pattern of mid-zonal damage in these animals is not typical of failure of oxidative metabolism and suggests that other mechanisms are involved.

Animals↗

PubMed1985

Is Werdnig-Hoffmann disease a pure lower motor neuron disorder?

It is not widely recognized that the pathology of Werdnig-Hoffman disease (WHD) may include cells other than the lower motor neuron. In the early infantile (acute) forms of this degenerative disease, neuropathologic involvement may extend well beyond the lower motor neuron territory to include neurons in spinal sensory ganglion and thalamus. The present report describes the neuropathologic findings of four patients with early infantile degenerative motor neuron disease, compares them to other reported patients, and discusses the relationship of these patients to those with classic WHD. We found involvement of thalamic and primary sensory neurons, although mild, to be a common finding in classic WHD. We suggest that early infantile forms of degenerative lower motor neuron disease which show prominent involvement of thalamic, primary sensory, and other neurons are but one end of the spectrum of WHD.

Brain↗

PubMed1985

Dissecting aneurysms of head and neck.

We analyzed four personal cases and 51 reported cases of dissecting aneurysms of the arteries of the head and neck. Subintimal dissection more commonly affects the intracranial vessels before age 40. In contrast, medial dissection tends to affect extracranial vessels after age 30. Vertebrobasilar dissection more variably affects either arterial plane. The reasons for these differing patterns of dissection are still not clear. In young subjects, the subintimal layer appears to be more susceptible; in contrast, the media becomes increasingly vulnerable with age, particularly in the presence of acquired medial disease.

Adolescent↗

PubMed1985

Neuropathology of oral-facial-digital syndromes.

A 3-month-old female infant with oral-facial-digital syndrome (OFD-I) was found to have extensive malformations of the brain and spinal cord. Our review of other case reports indicated that the most common central nervous system malformations found in OFD-I include cerebral epithelial (ependymal) cysts, agenesis of the corpus callosum, cerebral micropolygyria, and hypoplasia or dysplasia of the cerebellum, pons, and medulla. It is suggested that the individuals with OFD-I syndrome should be carefully studied clinically and pathologically for complex nervous system anomalies.

Abnormalities, Multiple↗

PubMed1984

Familial systemic carnitine deficiency.

Two sisters with systemic carnitine deficiency showed the heterogenicity of this condition and a lack of correlation between measurable carnitine levels and clinical manifestations. One child experienced recurrent metabolic encephalopathy, which was diagnosed as Reye's syndrome. The older child, despite lower carnitine concentrations, was asymptomatic. Lipid inclusion myopathy was shown in both children. Serum, muscle, and liver carnitine levels were reduced. The parents had normal serum carnitine concentrations. Both children had significantly abnormal renal handling of carnitine, and their mother, a mild alteration. This family provided evidence for genetic transmission and presumed autosomal recessive inheritance in this disease. Both children were treated with carnitine without clear benefit; no side effects were noted. Previously reported cases of systemic carnitine deficiency were reviewed.

Brain Diseases, Metabolic↗

PubMed1984

Computed tomographic findings in akinetic mutism.

Brain-injured children who progress from coma to a sleeplike state of akinetic mutism are often misinterpreted by their parents as having improved. In children with akinetic mutism caused by extensive destruction of the cerebral gray matter, the computed tomographic scan may demonstrate the irreversible nature of the pathologic changes.

Akinetic Mutism↗

PubMed1984

Cerebro-ocular dysplasia-muscular dystrophy (COD-MD) syndrome.

The Fukuyama form of congenital muscular dystrophy (FCMD), first described in Japan, is associated with distinct dysplastic cerebral malformations including agyria and micropolygyria of cerebral cortex, micropolygyria of cerebellum, and leptomeningeal gliomesodermal proliferations. We describe seven cases in four families from the United States with a syndrome similar to FCMD but with additional ophthalmic malformations. We believe that these cases represent a form of congenital muscular dystrophy different from FCMD and termed it cerebro-ocular dysplasia-muscular dystrophy (COD-MD) syndrome.

Abnormalities, Multiple↗

PubMed1984

Effects of steroidal and nonsteroidal antiinflammatory agents in neonatal endotoxemia.

The effects of steriodal and nonsteroidal antiinflammatory agents on mortality, plasma glucose and lactate levels, and pathologic alterations associated with Escherichia coli endotoxemia were assessed in neonatal rats. Animals were first injected subcutaneously with either high (LD95) or moderate (LD35) doses of endotoxin and immediately thereafter were administered either saline, dexamethasone, indomethacin, or glucose. Animals treated with saline or glucose developed significant hypoglycemia and hyperlactacidemia. Dexamethasone and indomethacin ameliorated the fall in glucose and the rise in lactate during high dose but not moderate dose endotoxemia. Pathologic changes consisting of widespread inflammation and hepatic necrosis were most marked in the saline- and indomethacin-treated animals. Only dexamethasone significantly reduced mortality at either LD95 or LD35 doses of endotoxin. We conclude that dexamethasone may reduce mortality in endotoxic shock through mechanisms other than simple amelioration of changes in plasma glucose.

Animals↗

PubMed1983

Focal necrosis of the spinal cord in utero.

We examined a child who suffered in utero necrosis of the spinal cord. Necrosis of this type typically occurs in the fetus with neck hyperextension and breech position and presumably results from focal ischemia of the spinal cord.

Cesarean Section↗